Project Summary/Abstract - The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study is an ongoing series of multi-site randomized controlled trials that provide empirical data to address ethical, social and translational issues in genetic susceptibility testing for common diseases. Such work has become increasingly important given the expansion of genome-wide association studies identifying genetic risk factors for common diseases and corresponding efforts to commercialize genetic testing using these markers. Our paradigm for these trials is disclosure of Apolipoprotein E (APOE) genotype as part of risk assessment for Alzheimer's disease (AD) to unaffected individuals. In previous funding cycles we have enrolled 1000 participants in three separate trials, and our multi-disciplinary team has been highly productive in analyzing many aspects of the psychological impact and health behavior changes of receiving genetic risk information. We now propose the first translational genetics study to focus upon the situation where mild early symptoms of a disease (phenotype) and known genetic marker (genotype) information can be used together to produce more imminent risk projections. To do this, we will develop genotype specific risk curves for patients with Mild Cognitive Impairment, a condition where the APOE epsilon 4 allele is associated with more rapid progression to AD and differential response to certain pharmacological treatments. We will carry out a new randomized clinical trial to examine the impact of imminent risk assessment (i.e., risk of conversion to AD within 3 years) in these individuals and their care partners. We also propose to develop and validate a novel instrument, which we call the Capacity Assessment Tool for Genetic Testing, to reliably assess an individual's capacity to consent to genetic testing, which will be useful for clinicians and researchers working with neuropsychiatric diseases. Finally, we propose to systematically study the long-term psychological impact and health behavior changes in participants who learned their APOE genotype in earlier cycles of the REVEAL Study, some of whom were enrolled as early as 2000. These data will help inform policy and practice regarding the use of genetic risk information for common, complex diseases. Public Health Relevance: REVEAL IV Project Narrative: In this continuation of the REVEAL Study, we will conduct a new randomized clinical trial to determine the psychological and health behavior changes associated with disclosing APOE genotype and 3-year risk estimates to persons with mild memory problems. We will also create a new instrument that clinicians and researchers can use to reliably evaluate a patient's capacity to consent to genetic testing and examine long-term impact of genetic risk assessment by following REVEAL Study patients 2-10 years following disclosure.